Plant-on-chip: Core morphogenesis processes in the tiny plant Wolffia australiana.

A plant can be thought of as a colony comprising numerous growth buds, each developing to its own rhythm. Such lack of synchrony impedes efforts to describe core principles of plant morphogenesis, dissect the underlying mechanisms, and identify regulators. Here, we use the minimalist known angiosperm to overcome this challenge and provide a model system for plant morphogenesis. We present a detailed morphological description of the monocot Wolffia australiana, as well as high-quality genome information. Further, we developed the plant-on-chip culture system and demonstrate the application of advanced technologies such as single-nucleus RNA-sequencing, protein structure prediction, and gene editing. We provide proof-of-concept examples that illustrate how W. australiana can decipher the core regulatory mechanisms of plant morphogenesis.

Investigation of Structure, Ionic Conductivity, and Electrochemical Stability of Halogen Substitution in Solid-State Ion Conductor Li3YBr x Cl6-x.

Li3YX6 (X = Cl, Br) materials are Li-ion conductors that can be used as solid electrolytes in all solid-state batteries. Solid electrolytes ideally have high ionic conductivity and (electro)chemical compatibility with the electrodes. It was proven that introducing Br to Li3YCl6 increases ionic conductivity but, according to thermodynamic calculations, should also reduce oxidative stability. In this paper, the trade-off between ionic conductivity and electrochemical stability in Li3YBr x Cl6-x halogen-substituted compounds is investigated. The compositions of Li3YBr1.5Cl4.5 and Li3YBr4.5Cl1.5 are reported for the first time, along with a consistent analysis of the whole Li3YBr x Cl6-x (x = 0-6) tie-line. The results show that, while Br-rich materials are more conductive (5.36 × 10-3 S/cm at 30 °C for x = 4.5), the oxidative stability is lower (∼3 V compared to ∼3.5 V). Small Br content (x = 1.5) does not affect oxidative stability but substantially increases ionic conductivity compared to pristine Li3YCl6 (2.1 compared to 0.049 × 10-3 S/cm at 30 °C). This work highlights that optimization of substitutions in the anion framework provide prolific and rational avenues for tailoring the properties of solid electrolytes.

Two new alkaloids produced by Dothideomycetes sp. BMC-101 isolated from the Magnolia grandiflora.

ABSTACTA total of 16 fungal strains were isolated from fresh leaves and flowers of Magnolia grandiflora and the EtOAc extracts of them were assayed for antitumor activities. Among these, the fungus Dothideomycetes sp. BMC-101 with broad spectrum inhibition was selected for further study. Four alkaloids (1-4) including two new compounds (2-(hydroxyimino)-3-phenylpropanoyl)-L-phenylalanine (1) and 8-Acetyl-bisdethiobis(methylsulfanyl)apoaranotin (4)) were isolated from Dothideomycetes sp. BMC-101. The structure of 1 was characterized with an oxime moiety formed by the condensation of two phenylalanines. To our knowledge, this is the first report on a fungal phenylalanine derivative with an oxime moiety.

[The Prognosis Assessment Value of Interim 18F-FDG PET/CT Imaging in the Chemotherapy of Diffuse Large B-cell Lymphoma].

OBJECTIVE: To investigate the prognostic value of interim 18F-FDG PET/CT in patients with diffuse large B-cell lymphoma (DLBCL). METHODS: A total of 97 patients with pathologically diagnosed DLBCL at Sichuan Cancer Hospital and Institute from March 2015 to June 2020 were enrolled in this retrospective study. Receiver operating characteristic analysis (ROC) was used to calculate the optimum maximum standard uptake value reduction ratio (△SUVmax%) cut-off value. The prognostic value of △SUVmax% and Deauville five-point scale (5-PS) in patients with DLBCL was compared, and the determined prognostic factors were analyzed. RESULTS: ROC curve indicated that the optimum △SUV max% cut-off value was 74.9%. Patients with △SUVmax%≥74.9% had a lower rate of progression or recurrence than those with △SUVmax% < 74.9% (both P<0.001). Meanwhile, patients with 5-PS score < 4 also had a lower rate of progression or recurrence than those with 5-PS score≥4 (both P<0.001). △SUVmax% and 5-PS had high specificity (83.7% vs 83.7%) and negative predictive value (87.3% vs 84.9%), while low sensitivity (56.0% vs 52.2%) and positive predictive value (53.8% vs 50.0%). △SUVmax% was more sensitive than 5-PS for the corresponding parameters (78.3% vs 76.2%). Univariate analysis showed that Ann Arbor stage, international prognostic index of National Comprehensive Cancer Network (NCCN-IPI), △SUVmax% and 5-PS were associated with TTP and PFS (all P<0.001). Multivariate analysis showed that △SUVmax% was an independent predictor of TTP and PFS (P=0.031, P=0.023). CONCLUSION: Both 5-PS and △SUVmax% can be used to evaluate the prognosis of DLBCL patients, but the predictive value of △SUVmax% is superior to that of 5-PS.

Isobavachalcone Induces Multiple Cell Death in Human Triple-Negative Breast Cancer MDA-MB-231 Cells.

Standardized treatment guidelines and effective drugs are not available for human triple-negative breast cancer (TNBC). Many efforts have recently been exerted to investigate the efficacy of natural compounds as anticancer agents owing to their low toxicity. However, no study has examined the effects of isobavachalcone (IBC) on the programmed cell death (PCD) of human triple-negative breast MDA-MB-231 cancer cells. In this study, IBC substantially inhibited the proliferation of MDA-MB-231 cells in concentration- and time-dependent manners. In addition, we found that IBC induced multiple cell death processes, such as apoptosis, necroptosis, and autophagy in MDA-MB-231 cells. The initial mechanism of IBC-mediated cell death in MDA-MB-231 cells involves the downregulation of Akt and p-Akt-473, an increase in the Bax/Bcl-2 ratio, and cleaved caspases-3 induced apoptosis; the upregulation of RIP3, p-RIP3 and MLKL induced necroptosis; as well as a simultaneous increase in LC3-II/I ratio induced autophagy. In addition, we observed that IBC induced mitochondrial dysfunction, thereby decreasing cellular ATP levels and increasing reactive oxygen species accumulation to induce PCD. These results suggest that IBC is a promising lead compound with anti-TNBC activity.

Trehalose prevents glyphosate-induced testicular damage in roosters via its antioxidative properties.

Glyphosate (GLY), an active ingredient of the most commonly used herbicide, when in crops and feed, is deleterious to male reproductive health. Trehalose (Tre), a naturally non-reducing disaccharide, is shown to counteract the adverse stresses due to its antioxidation effect. Thus, this study was designed to investigate whether Tre can improve GLY-induced testicular damage via suppressing oxidative stress. 60 healthy Hy-Line Brown breeder roosters were utilized to assess the protective effects of Tre supplementation against testicular oxidative damage caused by GLY. Data showed that Tre administration significantly alleviated GLY- induced reduction in testis weight, decreased GLY level in the testis tissues, and alleviated GLY-caused testicular pathological damage. Concurrently, GLY treatment significantly elevated serum malondialdehyde (MDA) and testicular reactive oxygen species (ROS) levels, decreased serum total anti-oxidation capacity (T-AOC), catalase (CAT), superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) levels, which were all notably reversed by Tre administration. Moreover, GLY- inhibited nuclear factor erythroid 2-related factor 2 (Nrf2) pathway in rooster testis, a master regulator of oxidative stress, was markedly recovered by Tre administration. In summary, these findings demonstrated that Tre can prevent GLY-induced testicular damage in roosters by ameliorating oxidative stress.

How do temperature, humidity, and air saturation state affect the COVID-19 transmission risk?

Environmental parameters have a significant impact on the spread of respiratory viral diseases (temperature (T), relative humidity (RH), and air saturation state). T and RH are strongly correlated with viral inactivation in the air, whereas supersaturated air can promote droplet deposition in the respiratory tract. This study introduces a new concept, the dynamic virus deposition ratio (α), that reflects the dynamic changes in viral inactivation and droplet deposition under varying ambient environments. A non-steady-state-modified Wells-Riley model is established to predict the infection risk of shared air space and highlight the high-risk environmental conditions. Findings reveal that a rise in T would significantly reduce the transmission of COVID-19 in the cold season, while the effect is not significant in the hot season. The infection risk under low-T and high-RH conditions, such as the frozen seafood market, is substantially underestimated, which should be taken seriously. The study encourages selected containment measures against high-risk environmental conditions and cross-discipline management in the public health crisis based on meteorology, government, and medical research.

The application of fluorescein sodium for the resection of medulloblastoma.

INTRODUCTION: Surgical resection of medulloblastoma (MB) remains a challenge. At present, a variety of tracers have been used for intraoperative tumor visualization. However, there are few reports on the intraoperative visualization of MB. Hence, we reported our experience of applying fluorescein sodium (FS) in MB surgery. METHODS: We retrospectively analyzed the clinical information of patients with MB confirmed by surgery and pathology from January 2016 to December 2020 from Sun Yat-sen University Cancer Center. A total of 62 patients were enrolled, of which 27 received intraoperative FS and 35 did not. The intraoperative dose of FS was 3 mg/kg. RESULTS: Among the 62 patients, 42 were males, and twenty were females. The age of onset in the FS group was 9.588 ± 7.322, which in the non-fluorescein sodium group was 13.469 ± 10.968, p = 0.198. We did not find significant differences in tumor location, tumor size, tumor resection, tumor histology, and preoperative symptoms (hydrocephalus, headache, vomit, balance disorder) between the groups. There was no significant difference in the postoperative symptoms (hydrocephalus, headache, vomiting, balance disorder, and cerebellar mutism). However, patients in the FS group had a relatively low incidence of balance disorder and cerebellar mutism. There was definite fluorescence of tumor in all cases of the FS group, and even the tiny metastatic lesion was visible. No case had side effects related to the use of FS. CONCLUSIONS: FS is safe and effective in MB surgery. Whether the application of FS for surgery can reduce complications remains to be studied in the future.

Ascorbic acid and hydrocortisone synergistically inhibit septic organ injury via improving oxidative stress and inhibiting inflammation.

BACKGROUND: The current study aimed to investigate the effect of the combination of ascorbic acid (AscA) and hydrocortisone (Hyd) on septic organ injury and its potential mechanism. METHOD: Sepsis was induced in mice by a single intraperitoneal injection of lipopolysaccharides. RESULTS: AscA and Hyd combined showed more effective protection of the injured liver and kidney in septic mice by decreasing alanine aminotransferase, aspartate aminotransferase, serum urea nitrogen, and serum creatinine and ameliorating pathological manifestations than Hyd or AscA alone. AscA showed a mild inhibitory effect on the secretion of proinflammatory cytokines (tumor necrosis factor-alpha (TNF-α), interleukin-1ß (IL-1ß), and interleukin-6 (IL-6)). However, Hyd showed a weak regulatory effect on septic oxidative stress markers (malondialdehyde (MDA), superoxide dismutase (SOD), and glutathione peroxidase (GSH-Px)). However, the combination of AscA and Hyd showed a more powerful inhibitory effect on the septic inflammatory response and oxidative stress than Hyd or AscA alone by decreasing TNF-α, IL-1ß, and IL-6 and regulating MDA, SOD, and GSH. In an in vitro study, cotreatment of RAW 264.7 macrophages with Hyd and AscA sharply reduced reactive oxygen species (ROS) generation and synergistically inhibited TNF-α, IL-1ß, and IL-6 secretion, which could be abolished by additional stimulation with the ROS donor 3-nitropropionic acid (3-NP). As expected, cotreatment of macrophages with Hyd and AscA synergistically inhibited the activation of p38 MAPK and p-p65, and the effect could be reversed by additional stimulation with 3-NP. CONCLUSIONS: AscA and Hyd synergistically protect the kidney and liver from injury by inhibiting the inflammatory response and oxidative stress. The powerful inhibitory effects of AscA on oxidative stress contribute to the synergistic anti-inflammatory action.

Carbon-free and binder-free Li-Al alloy anode enabling an all-solid-state Li-S battery with high energy and stability.

Incompatibility of electrolytes with Li anode impedes the application of solid-state batteries. Aluminum with appropriate potential, high-capacity, and electronic conductivity can alloy with Li spontaneously and is proposed herein as a carbon-free and binder-free anode of an all-solid-state Li-S battery (LSB). A biphasic lithiation reaction of Al with modest volume change was revealed by in situ characterization. The Li0.8Al alloy anode showed excellent compatibility toward the Li10GeP2S12 (LGPS) electrolyte, as verified by the steady Li0.8Al-LGPS-Li0.8Al cell operation for over 2500 hours at 0.5 mA cm-2. An all-solid-state LSB comprising Li0.8Al alloy anode and melting-coated S composite cathode functioned steadily for over 200 cycles with a capacity retention of 93.29%. Furthermore, a Li-S full cell with a low negative-to-positive ratio of 1.125 delivered a specific energy of 541 Wh kg-1. This work provides an applicable anode selection for all-solid-state LSBs and promotes their practical procedure.

Achieving long cycle life for all-solid-state rechargeable Li-I2 battery by a confined dissolution strategy.

Rechargeable Li-I2 battery has attracted considerable attentions due to its high theoretical capacity, low cost and environment-friendliness. Dissolution of polyiodides are required to facilitate the electrochemical redox reaction of the I2 cathode, which would lead to a harmful shuttle effect. All-solid-state Li-I2 battery totally avoids the polyiodides shuttle in a liquid system. However, the insoluble discharge product at the conventional solid interface results in a sluggish electrochemical reaction and poor rechargeability. In this work, by adopting a well-designed hybrid electrolyte composed of a dispersion layer and a blocking layer, we successfully promote a new polyiodides chemistry and localize the polyiodides dissolution within a limited space near the cathode. Owing to this confined dissolution strategy, a rechargeable and highly reversible all-solid-state Li-I2 battery is demonstrated and shows a long-term life of over 9000 cycles at 1C with a capacity retention of 84.1%.

Rice Cell Division Cycle 20s are required for faithful chromosome segregation and cytokinesis during meiosis.

Chromosome segregation must be under strict regulation to maintain chromosome euploidy and stability. Cell Division Cycle 20 (CDC20) is an essential cell cycle regulator that promotes the metaphase-to-anaphase transition and functions in the spindle assembly checkpoint, a surveillance pathway that ensures the fidelity of chromosome segregation. Plant CDC20 genes are present in multiple copies, and whether CDC20s have the same functions in plants as in yeast and animals is unclear, given the potential for divergence or redundancy among the multiple copies. Here, we studied all three CDC20 genes in rice (Oryza sativa) and constructed two triple mutants by clustered regularly interspaced short palindromic repeats (CRISPR)/CRISPR-associated protein 9-mediated genome editing to explore their roles in development. Knocking out all three CDC20 genes led to total sterility but did not affect vegetative development. Loss of the three CDC20 proteins did not alter mitotic division but severely disrupted meiosis as a result of asynchronous and unequal chromosome segregation, chromosome lagging, and premature separation of chromatids. Immunofluorescence of tubulin revealed malformed meiotic spindles in microsporocytes of the triple mutants. Furthermore, cytokinesis of meiosis I was absent or abnormal, and cytokinesis II was completely prevented in all mutant microsporocytes; thus, no tetrads or pollen formed in either cdc20 triple mutant. Finally, the subcellular structures and functions of the tapetum were disturbed by the lack of CDC20 proteins. These findings demonstrate that the three rice CDC20s play redundant roles but are indispensable for faithful meiotic chromosome segregation and cytokinesis, which are required for the production of fertile microspores.

κ-Carrageenan Oligosaccharides Inhibit the Inflammation of Lipopolysaccharide-Activated Microglia Via TLR4/NF-κB and p38/JNK MAPKs Pathways.

Microglial inflammation plays an essential role in neurodegenerative disease. Our previous studies had shown that κ-carrageenan oligosaccharides (KOS) could inhibit the excessive activation of microglia that induced by LPS, while the interrelated mechanisms were still indistinct. Therefore, we detected the inflammatory signaling pathway on LPS-activated microglia that pretreat by different content of KOS to reveal the mechanism on KOS's inhibition of microglia inflammatory response. ELISA was used to detect the effects of KOS on the secretion of interleukin-1 (IL-1ß), tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6) and prostaglandin E2 (PG-2) by LPS-activated microglia, respectively. The production of reactive oxygen species (ROS) and nitric oxide (NO) in microglia cells was detected by flow cytometry, and the protein expression of immunoinflammation-related signaling pathways were detected by Western Blot. The results showed that KOS could significantly protected the microglia from the over-activated inflammatory by inhibiting the release of inflammatory cytokines and the oxidative stress response. And KOS could reduce the expression of the protein that related to the TLR4/NF-κB and p38/JNK MAPKs pathways activated by LPS in microglia. However, there may be no specific target of KOS in cells. Therefore, KOS, a natural algal source oligosaccharide, has immunomodulatory effects and can be used as a potential intervention therapy for inflammatory related neurodegenerative diseases.

Functional connectivity analysis of sensory motor network in patients with bipolar disorder type Ⅰ / 中华行为医学与脑科学杂志

Objective:To analyze the functional connectivity (FC) characteristics of sensory motor network (SMN) in patients with bipolar disorder type Ⅰ (BD-Ⅰ) by independent component analysis (ICA), and explore the correlation between abnormal SMN and clinical symptoms.Methods:Eighteen patients with BD-Ⅰ (BD-Ⅰ group) and 20 matched normal controls (HC group) were included.Both groups received resting state fMRI (rs-fMRI) scanning.Based on ICA-fMRI data, one-sample t-test and two-sample t-test were used to analyze the components of SMN and to explore abnormal brain regions between the two groups.Functional network analysis (FNC) was also used to explore the functional connectivity between SMN and other brain networks.Pearson correlation analysis were conducted by SPSS 17.0 to measure the potential associations between intra-and inter-network functional connectivity and age, education, score of Bech-Rafaelsen mania rating scale (BRMS), score of positive and negative syndrome scale (PANSS) and other indicators. Results:In BD-Ⅰ group, the functional connection in the right paracentral lobule (MIN: x=8, y=-32, z=68, t=4.86, P<0.001) and the right postcentral gyrus (MIN: x=41, y=-26, z=53, t=3.33, P<0.001) in SMN were higher than those in HC group.Compared with HC group, the connectivity value in patients with BD-Ⅰ increased between SMN-DAN (0.247±0.073, -0.078±0.080, t=-2.974, P<0.01, FDR adjusted), while the connectivity value decreased between SMN-DMN(-0.037±0.054, 0.272±0.067, t=3.520, P<0.01, FDR adjusted) and between SMN-rFPN(-0.034±0.055, 0.231±0.070, t=2.939, P<0.01, FDR adjusted). Conclusion:The sensorimotor network of patients with BD-Ⅰ has abnormal functional connections within and between networks, and FC values in some networks are positively correlated with manic symptoms, which may be part of the neural mechanisms of patients with BD-Ⅰ.

Histone demethylase JMJD3 downregulation protects against aberrant force-induced osteoarthritis through epigenetic control of NR4A1 / 国际口腔科学杂志·英文版

Osteoarthritis (OA) is a prevalent joint disease with no effective treatment strategies. Aberrant mechanical stimuli was demonstrated to be an essential factor for OA pathogenesis. Although multiple studies have detected potential regulatory mechanisms underlying OA and have concentrated on developing novel treatment strategies, the epigenetic control of OA remains unclear. Histone demethylase JMJD3 has been reported to mediate multiple physiological and pathological processes, including cell differentiation, proliferation, autophagy, and apoptosis. However, the regulation of JMJD3 in aberrant force-related OA and its mediatory effect on disease progression are still unknown. In this work, we confirmed the upregulation of JMJD3 in aberrant force-induced cartilage injury in vitro and in vivo. Functionally, inhibition of JMJD3 by its inhibitor, GSK-J4, or downregulation of JMJD3 by adenovirus infection of sh-JMJD3 could alleviate the aberrant force-induced chondrocyte injury. Mechanistic investigation illustrated that aberrant force induces JMJD3 expression and then demethylates H3K27me3 at the NR4A1 promoter to promote its expression. Further experiments indicated that NR4A1 can regulate chondrocyte apoptosis, cartilage degeneration, extracellular matrix degradation, and inflammatory responses. In vivo, anterior cruciate ligament transection (ACLT) was performed to construct an OA model, and the therapeutic effect of GSK-J4 was validated. More importantly, we adopted a peptide-siRNA nanoplatform to deliver si-JMJD3 into articular cartilage, and the severity of joint degeneration was remarkably mitigated. Taken together, our findings demonstrated that JMJD3 is flow-responsive and epigenetically regulates OA progression. Our work provides evidences for JMJD3 inhibition as an innovative epigenetic therapy approach for joint diseases by utilizing p5RHH-siRNA nanocomplexes.

Analysis on clinical and genetic characteristics of children with ATP-sensitive potassium channel congenital hyperinsulinism / 中华胰腺病杂志

Objective:To analyze clinical characteristics and genetic characteristics of children with ATP sensitive potassium passage (K ATP-HI). Methods:Forty-five children with genetically confirmed K ATP-HI and their families admitted to Beijing Children′s Hospital of Capital Medical University between February 2002 and December 2018 were selected as the study subjects. A detailed retrospective analysis of the patient's clinical characteristics, diagnosis and treatment process, disease-causing gene carrying status and later follow-up data was performed. ABCC8/KCNJ11 gene was sequenced by second-generation sequencing technology. Results:Among 45 children with K ATP-HI, 34 cases (75.6%) were neonatal onset, the first symptoms of 21 cases (46.7%) were convulsions. 39 cases had been treated with diazoxide, including 12 cases (30.8%) with good efficacy, 16 cases (41%) with poor efficacy and 11 cases with uncertain efficacy. Octreotide was further applied in 18 patients with uncertain or ineffective efficacy after diazoxide treatment, and 13 cases (72.2%) were effective, 3 cases were ineffective, and 2 cases were uncertain. 10 CHI patients who were ineffective to drug treatment or had clearly focal lesions confirmed by 18F-dopa positron emission by computed tomography ( 18F-DOPA PET) scans had undergone surgical treatment, 8 of which underwent partial pancreatectomy and blood glucose returned to normal after the operation; the other 2 cases underwent subtotal pancreatectomy and both had secondary diabetes after operation. Among 45 children with K ATP-HI, 1 case carried both ABCC8 and KCNJ11 mutations, 10 cases carried ABCC8 compound heterozygous mutations, and the remaining 34 cases carried ABCC8/KCNJ11 single genetic mutation. Among them, 21 cases had paternal inheritance, and 3 cases had maternal inheritance, 6 cases were identified with de novo mutations. Conclusions:Diazoxide treatment was ineffective for most K ATP-HI children, but octreotide had a higher effective rate. Partial pancreatectomy for focal type patients had a higher cure rate, and there was a risk of secondary diabetes after subproximal pancreatectomy, so it was very important to clarify the histological type of children before surgery. ABCC8 gene mutations and KCNJ11 gene mutations were the main pathogenic genes of K ATP-HI. Among patients carrying mutations in single ABCC8 or KCNJ11 gene mutation, K ATP-HI inherited by paternity were the majority. Some K ATP-HI children can relieve the hypoglycemia symptoms by themselves.

Exploring the effects of artesunate and fuzheng huayu decoction on mitochondria in the treatment of schistosomiasis liver fibrosis / 中华肝脏病杂志

Objective: To compare the effects of artesunate (Art) and fuzheng huayu decoction on mitochondrial autophagy in the treatment of schistosomiasis liver fibrosis. Methods: Eighty C57BL/6 female mice were randomly divided into healthy control group, infection group, Art treatment group and Fuzheng Huayu Decoction treatment group, with 20 mice in each group. Mice in the infection group and treatment group were infected with 16 Schistosoma japonicum cercariae. After 6 weeks, praziquantel (300 mg/kg) was used for 2 days to kill the worms. The Art treatment group was treated with intraperitoneal injection of 100 mg/kg/day, while the Fuzheng Huayu Decoction treatment group was fed 16g of fuzheng huayu decoction per 1kg per day. After 6 weeks, fresh liver tissues of the four groups were collected. Masson staining and Western blot were used to observe the succinate dehydrogenase subunit A (SDHA) and malate dehydrogenase (MDH2), citrate synthase (CS), ketoglutarate dehydrogenase (OGDH), and target of rapamycin 1 (mTORC1) pathway involved in mitochondrial tricarboxylic acid cycle in liver tissues. The relative expression levels of adenylate activated protein kinase (AMPK) and mitochondrial autophagy pathway kinase (PINK1) were detected. Liver tissue samples were extracted from each group to detect the mitochondrial oxygen consumption rate. Two-way ANOVA was used to compare the significance and difference between two sets of samples. Results: Masson staining showed that the infection group mice had significantly higher liver fibrosis area than the healthy control group, while the Art treatment group and Fuzheng Huayu Decoction treatment group mice had lower liver fibrosis area than the infection group. Western blot analysis showed that the infection group (0.82 ± 0.05) had significantly lower relative expression of SDHA protein than the healthy control group (1.00 ± 0.05) (t = 11.23, P = 0.0035), while the Art treatment group (0.73 ± 0.05) had significantly higher relative expression of SDHA protein than the infection group (t = 10.79, P = 0.0073). However, there was no significant change in Fuzheng Huayu Decoction treatment group (0.98±0.05) (t = 1.925, P = 0.1266). The relative expression of p-AMPK protein was significantly higher in the infection group (1.15 ±0.05) than in the healthy control group (0.98 ± 0.07, t = 12.18, P = 0.0029), and the expression of p-AMPK in the Art treatment group (0.50 ± 0.05) was significantly lower than the infection group (t = 11.78, P = 0.0032). The relative protein expression of AMPK was significantly lower in the infection group (0.80 ± 0.05) than in the healthy control group (1.00 ± 0.05, t = 10.53, P = 0.0046). The expression of AMPK was significantly lower in the Art treatment group (0.54 ± 0.05) than in the infection group (T = 13.98, P = 0.0036). The relative expression of p-mTORC1 protein (0.93 ± 0.08) was not significantly different in the infection group than in the healthy control group (t = 2.28, P = 0.065), while the Art treatment group (0.63 ± 0.05) had significantly lower relative expression of p-mTORC1 protein than the infection group (t = 10.58, P = 0.029). The expression of p-mTORC1/ m-TORC1 was not significantly different in the infection group (0.98 ± 0.03) than in the healthy control group (0.97 ± 0.03, t = 0.98, P = 0.085), while the Art treatment group (0.63 ± 0.05) had significantly lower relative expression of p-mTORC1/ m-TORC1 than the infection group (t = 14.58, P = 0. 009). The relative protein expression of PINK1 was significantly lower in the infection group (0.55 ± 0.05) than in the healthy control group (1.00 ± 0.03, t = 13.49, P = 0.0011), while the Art treatment group (1.21 ± 0.05, t = 9.98, P = 0.0046) and Fuzheng Huayu Decoction treatment group (1.31 ±0.35, t = 6.98, P = 0.027) had significantly higher relative protein expression of PINK1 than the infection group. Mitochondrial function tests showed that after adding substrate complex II, the oxygen consumption of the infection group was lower than the healthy control group, while the Art treatment group and the Fuzheng Huayu Decoction treatment group had higher oxygen consumption than the infection group. The oxygen consumption was significantly lower after adding the substrate complex III in the infection group than the healthy control group, while the Art treatment group and Fuzheng Huayu Decoction treatment group had higher oxygen consumption than the infection group. Conclusion: Art can alleviate schistosomiasis liver fibrosis by inhibiting AMPK/mTORC1 signaling pathway activity and enhancing mitochondrial oxygen consumption, autophagy and SDHA expression.

The in vivo imaging of zebrafish for chemical vascular toxicity assessment / 中华预防医学杂志

Objective: To evaluate the vascular toxicity of chemicals by a real-time observation approach using the transgenic zebrafish. Methods: The spatiotemporal vascular alterations of transgenic zebrafish after chemical exposure were assessed by laser confocal microscopy and high-content screening analysis, respectively. Results: The method using Laser Confocal Microscopy (LCM) is easier to operate and yields high-resolution images, while it is lower throughput and inefficient. In contrast, high-content analysis (HCA) analysis obtains high-quality data of vascular toxicity manifesting whole blood vasculature, whereas it requires delicate operation procedures and advanced experimental conditions. Conclusion: Two kinds of zebrafish imaging methods each have advantages and disadvantages. LCM is suitable for the evaluation of a small number of chemicals. HCA, a cutting-edge technology, has great potential for chemical safety assessment allowing high throughput vascular toxicity tests of a good number of chemicals at a time.

Isobavachalcone induces cell death through multiple pathways in human breast cancer MCF-7 cells / 南方医科大学学报

OBJECTIVE@#To explore the effects of isobavachalcone (IBC) on cell death of human breast cancer MCF-7 cells and explore the possible mechanism.@*METHODS@#MCF-7 cells were treated with different concentrations of IBC, and the changes in cell proliferation were assessed using MTT assay. Apoptosis of MCF-7 cells following treatment with 10, 20, and 40 μmol/L IBC was analyzed using flow cytometry with annexin V-FITC/PI double staining and fluorescence microscopy, and the expressions of apoptosis- and autophagy-related proteins (Bax, Bcl-2, Akt, p-Akt, p62, and LC3) were detected with Western blotting. Electron microscopy was used to observe the changes in submicrostructure of the cells following treatment with 40 μmol/L IBC. JC-1 assay kit, ATP assay kit, and reactive oxygen species (ROS) kit were used to determine the effect of IBC on mitochondrial function of the cells.@*RESULTS@#MTT assay showed that IBC significantly inhibited the proliferation of MCF-7 cells in a concentration- and time-dependent manner, with IC50 values of 38.46, 31.31, and 28.26 μmol/L at 24, 48, and 72 h, respectively. IBC also concentration-dependently induced apoptosis of MCF-7 cells. IBC-induced cell death was inhibited by z-VAD-fmk, a caspase inhibitor (P < 0.05), but not by the necroptosis inhibitor necrostatin-1 (Nec-1). Western blotting showed that IBC-induced MCF-7 cell apoptosis by increasing Bax expression and down-regulating the expressions of Bcl-2, Akt and p-Akt-473 (all P < 0.05). With the increase of IBC concentration, the expression of autophagy-related protein p62 and the LC3-II/I ratio increased progressively. Electron microscopy revealed the presence of autophagic bodies in IBC-treated MCF-7 cells. IBC treatment also resulted in decreased mitochondrial membrane potential and intracellular ATP level and increased ROS accumulation in MCF-7 cells (P < 0.05).@*CONCLUSION@#IBC is capable of inducing both apoptosis and autophagy in MCF-7 cells, suggesting the potential value of IBC as a lead compound in the development of anti-breast cancer agents.